Computer simulations using ab initio (density functional theory based) Car-Parinello molecular dynamics (CPMD) and hybrid quantum CPMD / classical MD methodologies are proposed to complement experimental programs at the University of Pennsylvania and elsewhere that focus on enzyme catalysis. The objective of the present proposal is to use state-of-the-art computational methods to explore in detail selected examples of enzymes that exploit the bridged bimetal motif for catalysis. Specifically, mechanistic models of Aeromonas proteolytica aminopeptidase (AAP) and arginase will be examined, as well as the structural and dynamical properties of biomimetic variants. The computational studies will investigate the metal and substrate selectivity of hydrolytic enzymes (AAP), and compare the redox catalase activity of manganese catalase and arginase. In addition, the catalytic mechanism of methane monooxygenase (MMO) will be explored along with modeling the hydrogen peroxide disproportionation and oxygen activation processes at the bimetal core of a biomimetic MMO protein. The long-term goal is to reach a deep understanding of the role of, as well as the fine tuning at, the bridged bimetal motif in redox and hydrolytic enzymatic catalysis. This understanding will be based on a systematic comparative approach to a common motif present in different environments and promoting different reaction processes. The wealth of available experimental data on the bimetal motif lends itself to a controlled study, whose value will be further enhanced by the possibility of suggesting new experiments and ultimately contributing to the design of therapies that target such enzymes.